Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study.

Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. The study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432 . Date of registration: 08.03.2016. Retrospectively registered

Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool.

Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction. From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model. Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p<0.02, sensitivity>0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p<0.02). The association of MBT and CRS-R scoring improves significantly the evaluation of consciousness and the predictability of outcome in the acute phase. Subtle motor behaviour assessment provides accurate insight into the amount and the content of consciousness even in the case of cognitive motor dissociation

La fatigue chez le patient cérébrolésé et son impact sur la réinsertion socioprofessionnelle [Fatigue after acquired brain injury and its impact on socio-professional reintegration]

Patients with acquired brain injury often suffer from pathological fatigue that differs from "normal" fatigue in that it appears more quickly and during non-demanding tasks, and recovery is not complete despite rest. It limits physical and cognitive activities, interferes with rehabilitation and return to work. The underlying mechanisms are poorly understood but appear to involve dysfunction of brain interactions. Current management combining physical reconditioning, cognitive compensatory strategies, and treatment of associated factors often leads to significant clinical improvement and promotes socio-professional reintegration. However, the effect remains insufficient in some patients, which underlines the importance of developing new therapeutic approaches based on a better understanding of the underlying neuronal deficits

From disorders of consciousness to early neurorehabilitation using assistive technologies in patients with severe brain damage.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the latest challenges addressed by neurorehabilitation initiated very early after the brain damage, such as dealing with disorders of consciousness in terms of diagnosis, prognosis and rehabilitative treatment, or determining best timing for first rehabilitative intervention, best therapeutic approaches and best modalities. RECENT FINDINGS: Early management of patients with severe brain damage requires a multidisciplinary rehabilitative approach that encompasses clinical skills in various fields, standard therapies, and assistive technologies.Despite a high rate of misdiagnosis and poor outcome prediction in disorders of consciousness, the observation of subtle motor signs may be a promising way to reach accurate diagnosis and better outcome prediction. Neurosensory stimulation remains the current treatment to promote emergence from disorders of consciousness.Early timing of neurological rehabilitation is definitively efficient, but a safety period should be respected. Some standard therapies and assistive technologies have demonstrated explicit evidence in neurological recovery and high treatment dose is needed to emphasize the therapeutic effect, but several controversies persist in treatment evidence. SUMMARY: Current advancements have provided growing evidence for early neurorehabilitation, which should be definitively applied, but further studies are explicitly needed to diminish persistent controversies in the field

The role of parieto-temporal connectivity in pure neglect dyslexia.

The initial stages of reading are characterised by parallel and effortless access to letters constituting a word. Neglect dyslexia is an acquired reading disorder characterised by omission or substitution of the initial or the final letters of words. Rarely, the disorder appears in a'pure' form that is, without other signs of spatial neglect. Neglect dyslexia is linked to damage involving the inferior parietal lobe and regions of the temporal lobe, but the precise anatomical basis of the pure form of the disorder is unknown. Here, we show that pure neglect dyslexia is associated with decreased structural connectivity between the inferior parietal and lateral temporal lobe. We examined patient DM, who following bilateral occipito-parietal damage presented left neglect dyslexia together with right visual field loss, but no signs of spatial neglect. DM's reading errors were affected by word length and were much more frequent for pseudowords than for existing words. Most errors were omissions or substitutions of the first or second letter, and the spatial distribution of errors was similar for stimuli presented left or right of fixation. The brain lesions of DM comprised the inferior and superior parietal lobule as well as the cuneus and precuneus of the left hemisphere, and the angular gyrus and lateral occipital cortex of the right hemisphere. Diffusion tensor imaging revealed bilateral decrease of fibre tracts connecting the inferior parietal lobule with the superior and middle temporal cortex. These findings suggest that parieto-temporal connections play a significant role for the deployment of attention within words during reading

Hemodynamic Changes May Indicate Vessel Wall Injury After Stent Retrieval Thrombectomy for Acute Stroke.

Stent retrievers have revolutionized endovascular treatment of acute ischemic stroke (AIS). Animal studies showed that mechanical thrombectomy (MT) may cause endothelial injury and intimal layer edema. Using transcranial color-coded duplex-sonography (TCCS) we observed postprocedural hemodynamic changes in the treated vessel. We studied AIS patients with large intracranial artery occlusion in whom MT with stent retrievers was performed. Only those with complete recanalization (modified TICI-2b or 3) as assessed by postprocedural digital subtraction angiography (DSA) and in whom early control TCCS was performed were retained. Patients treated with intra-arterial thrombolysis or stenting were excluded. In 31 patients treated within a time period of 4 years (29 with middle cerebral artery [MCA] and 2 with basilar artery [BA] occlusion), postacute stroke brain-DSA confirmed complete recanalization without residual stenosis or vasospasm. However, in 27 (17 men, mean age 66.3 years) of them TCCS (mean 3.4 days after MT) showed very segmental acceleration of blood flow velocities in the affected arteries (MCA maximum peak systolic velocity [PSVmax] at least >35% as compared to the contralateral side at the same depth; BA PSVmax >40% as compared to velocities at different depths of the same vessel). None showed clinical deterioration. TCCS follow-up (mean 20 days) showed normalization in 14 of 16 cases. Our TCCS study provides preliminary evidence of focal acceleration of blood flow velocities after MT. Without residual stenosis or vasospasm, this may be a sign of endothelial layer disruption/intimal injury. Further studies are needed to confirm our results

Neurosensory stimulation outdoors enhances cognition recovery in cognitive motor dissociation: A prospective crossover study.

Neurosensory stimulation is effective in enhancing the recovery process of severely brain-injured patients with disorders of consciousness. Multisensory environments are found in nature, recognized as beneficial to many medical conditions. Recent advances detected covert cognition in patients behaviorally categorized as un- or minimally responsive; a state described as cognitive motor dissociation (CMD). To determine effectiveness of a neurosensory stimulation approach enhanced by outdoor therapy, in the early phases of recovery in patients presenting with CMD. A prospective non-randomized crossover study was performed. A two-phase neurosensory procedure combined identical individually goal assessed indoor and outdoor protocols. All sessions were video-recorded and observations rated offline. The frequency of volitional behavior was measured using a behavioral grid. Fifteen patients participated in this study. The outdoor group patients had statistically significant higher number of intentional behaviors than the indoor group on seven features of the grid. Additionally, for all items assessed, total amount of behaviors in the outdoor condition where higher than those in the indoor condition. Although preliminary, this study provides robust evidence supporting the effectiveness and appropriateness of an outdoor neurosensory intervention in patients with covert cognition, to improve adaptive goal-oriented behavior. This may be a step towards helping to restore functional interactive communication

GnRH replacement rescues cognition in Down syndrome.

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS